ARTEMIS-008：HS-20093 Compared With Topotecan in Subjects With Relapsed Small Cell Lung Cancer

This is a phase 3, randomized, open-label, multicenter study comparing HS-20093 with topotecan in patients with limited or extensive SCLC that had disease progression on or after first-line platinum-based regimen. Subjects will be randomized by a ratio of 1:1 to receive HS-20093 or topotecan until disease progression.

The primary objective of this study is to assess whether treatment with HS-20093 prolongs OS compared with treatment of topotecan among subjects with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of HS-20093. The exploratory objectives are to characterize the pharmacokinetics of HS-20093, evaluate E-R relationship, immunogenicity of HS-20093, B7-H3 protein expression and soluble B7-H3 expression.

Inclusion criteria

• Male or female subjects ≥18 years of age.
• Histologically or cytologically confirmed SCLC.
• Subjects who progressed on or after first-line platinum-based regimens.
• Has at least 1 measurable lesion as defined per RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Minimum life expectancy of more than 12 weeks.
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential.
• Men or women should be using adequate contraceptive measures throughout the study.
• Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.

Exclusion criteria

• Combined SCLC, any previous diagnosis of transformed SCLC or SCLC that has transformed to NSCLC.
• Chemotherapy-free interval ≤30 days.
• Has received prior treatment with anti-B7 homologue 3 (B7-H3) targeted agents.
• Has received prior treatment with topoisomerase I inhibitor, including ADC that consists of topoisomerase I inhibitor.
• Has inadequate washout period before randomization as specified in the protocol.
• Untreated or symptomatic brain metastases with exceptions defined in the protocol.
• Unresolved toxicity from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 with exceptions defined in the protocol.
• History of other malignancy with exceptions defined in the protocol.
• Inadequate bone marrow reserve or organ dysfunction.
• Evidence of cardiovascular risks.
• Severe, uncontrolled or active cardiovascular diseases.
• Severe or uncontrolled diabetes.
• Severe or uncontrolled high blood pressure.
• Clinically significant bleeding or obvious bleeding tendency within 1 month before randomization.
• Severe arterial or venous thromboembolic events within 3 months prior to randomization.
• Severe infections within 4 weeks before randomization.
• Receiving systemic corticosteroid therapy within 30 days prior to randomization with exceptions defined in the protocol.
• The presence of active infectious diseases before randomization.
• Current hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis.
• History of interstitial lung disease, immunotherapy-induced pneumonitis, clinically moderate or severe pulmonary disease.
• History of severe neuropathy or mental disorders.
• Female subjects of childbearing potential; female subjects who are breastfeeding or who plan to breastfeed while on study; female subjects planning to become pregnant while on study.
• Vaccination or hypersensitivity of any level within 4 weeks before randomization.
• History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins.
• Hypersensitivity to any ingredient of HS-20093, DNA topoisomerase I inhibitor or regimens of Topotecan.